DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.

A novel 18 F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-18 F-fluoropropoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of 18 F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. Methods: Tracer accumulation in the heart was studied over time after intravenous administration of 18 F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n 5 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n 5 4), or saline control (intravenously; n 5 4). Results: 18 F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the 18 F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved 18 F-LMI1195 uptake after desipramine pretreatment. Conclusion: In rats, cardiac uptake of 18 F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting 18 F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

Canine experiments were designed to determine if both histamine H1 and H2 receptors are present in the renal circulation. Renal blood flow (RBF) increased steeply over the first minute of intra-arterial histamine infusion, then increased gradually to a plateau in 3--5 min. Infusion of either histamine + H2 antagonist or of H1 agonist produced the initial rapid increase in RBF, whereas infusion of either histamine + H1 antagonist or of H2 antagonist produced a slower but more sustained increase in RBF. Histamine significantly increased urine flow rate (V), chloride excretion, and glomerular filtration rate (GFR). Infusion of the H2 agonist also increased V and Cl excretion without affecting GFR. By contrast H1 agonist significantly reduced V and Cl excretion and tended to reduce GFR (P less than 0.1 greater than 0.05). Histamine, H1 agonist, and H2 agonist each increased inner cortical more than outer cortical blood flow. These data suggest that 1) H1 and H2 receptors are present in the renal vasculature, 2) changes in intrarenal blood flow distribution are not responsible for histamine-induced diuresis, and 3) H1 receptors are primarily postglomerular while H2 receptors exhibit both pre- and postglomerular distribution.